Phylogenetic analysis of 45 enterovirus 71 (EV71) isolates for 6 years in Yamagata, Japan, clarified that the annual outbreak of hand-foot-and-mouth disease was due to four genetically distinct subgenogroups, including a novel "B5." Our results suggest that the importation of EV71 from surrounding countries has had a major epidemiological impact on the local community used in our study.

Long-term virus shedding after the disappearance of clinical symptoms was observed. Caution should be exercised when handling the excrement of infants and young children infected with NV.

No abstract

CYP2C19 genotype had an impact on the efficacy of clobazam, thus indicating that N-clobazam plays an important role in long-term clobazam therapy.

A nonlinear mixed-effect modeling (NONMEM) program was used to evaluate the effects of cytochrome P450 (CYP) 2C9 and CYP2C19 polymorphisms on the phenobarbital (PB) population clearance for Japanese epileptics. The pharmacokinetics of the 260 PB concentrations at a steady-state obtained from 79 patients was described with a one-compartment open pharmacokinetic model with first-order elimination. The covariates screened included the total body weight (BW), age, gender, PB daily dose, CYP2C9 and CYP2C19 genotypes, the coadministered antiepileptic drugs (AEDs), and complications. The final model of PB apparent clearance was as follows: CL = 0.23 x (BW/40)0.21 x 0.52CYP2C9*1/*3 x 0.68VPA x 0.85PHT x 0.85SMID x (1 + etaCL) where CL = the clearance of PB; CYP2C9*1/*3 = 1, otherwise 0; VPA = 1 if valproic acid is coadministered, otherwise 0; PHT = 1 if phenytoin is coadministered, otherwise 0; SMID = 1 if complications of severe or profound mental retardation with a significant behavior impairment are presented, otherwise 0; and etaCL = the independent random error distributed normally with the mean zero and variance equal to omegaP2. The total clearance of PB decreased by 48% in patients with CYP2C9*1/*3 genotype in comparison with those with CYP2C9*1/*1 genotype (P < 0.001). An effect of CYP2C19 polymorphisms was not detected. To our knowledge, this is the first report to demonstrate that the CYP2C9 genotype affects the PB metabolism in routine care, but the results should be further verified in other ethnic populations.

Reverse genetics has been documented for influenza A, B, and Thogoto viruses belonging to the family Orthomyxoviridae. We report here the reverse genetics of influenza C virus, another member of this family. The seven viral RNA (vRNA) segments of C/Ann Arbor/1/50 were expressed in 293T cells from cloned cDNAs, together with nine influenza C virus proteins. At 48 h posttransfection, the infectious titer of the culture supernatant was determined to be 2.51 ؋ 10 3 50% egg infectious doses/ml, which is lower than the number of influenza C virus-like particles (VLPs) (10 6 /ml) generated using the same system. By generating influenza C VLPs containing a given vRNA segment, we showed that each of the vRNA segments was similarly synthesized in the plasmid-transfected cells but that some segments were less efficiently incorporated into the VLPs. This finding leads us to speculate that the differences in incorporation efficiency into VLPs between segments might be a reason for the inefficient production of infectious viruses. Second, we generated a mutant recombinant virus, rMG96A, which possesses an Ala3Thr mutation at residue 24 of the M1 protein, a substitution demonstrated to be involved in the morphology (filamentous or spherical) of the influenza C VLPs. As expected, rMG96A exhibited a spherical morphology, whereas recombinant wild-type of C/Ann Arbor/1/50, rWT, exhibited a mainly filamentous morphology. Membrane flotation analysis of the cells infected with rWT or rMG96A revealed a difference in the ratio of membrane-associated M1 proteins, suggesting that the affinity of M1 protein to the cell membrane is a determinant for virion morphology.

No abstract

These findings suggested that GSTM1- rather than GSTM1-/T1- was a risk factor for carbamazepine-induced mild hepatotoxicity.